Marian Freedman

Swedish researchers found that many children and young adults who are prescribed melatonin are still taking it 3 years later and at larger doses.

Using registry data for an urban area centered around Stockholm, the authors determined that 9980 individuals up to aged 25 years were dispensed melatonin in 2016. Most patients (65%) had a neuropsychiatric diagnosis, and only 20% had a sleep disorder.

Prevalence of dispensed melatonin was 0.2% in preschoolers 5 years and younger, 1.4% in children aged 6 to 12 years, 3.4% in adolescents aged 13 to 17 years, and 1.2% in those aged 18 to 25 years.

Comorbid conditions were common, as was polypharmacy, identified in 4567 individuals (46%), more often females than males. Of those who began taking melatonin in 2016, 50% of male patients and 40% of female patients continued to use it throughout the following 3 years, often at increased doses.

I, too, would like to see some long-term studies. But given that sleep difficulties are major problems for children and their families, especially when combined with developmental disabilities such as autism, I continue to use melatonin in high doses if needed for these families. For neurotypical children, however, my go-to remains behavioral interventions.

Tedroff K, von Euler M, Dahlén E. Melatonin usage in children and young adults, a registry-based cohort study. 

 2022;39(30-34). doi:10.1016/j.ejpn.2022.05.007

Articles

Many children continue to use melatonin for years after being prescribed the medication, according to a recent study.

Long-term melatonin use in children: Is it safe? 

Only 3.6% of fully vaccinated febrile children with sickle cell disease (SCD) who visited an emergency department were found to have a serious bacterial infection (SBI) meriting hospitalization, according to a retrospective study in Saudi Arabia.

Investigators screened medical records associated with 833 febrile events, resulting in 40 study participants with positive bacterial culture results from various body fluids. The authors assessed the 30 febrile events for the remaining children and concluded that their hospitalization was justified. All these children were younger than 12 years and had received recommended vaccinations, including 13-valent pneumococcal conjugate vaccine, quadrivalent meningococcal conjugate vaccine, and 

type b vaccine, as well as regular penicillin prophylaxis. Additionally, most (57%) participants were male.

Urinary tract infection was the most prevalent SBI, seen in 2.2% of participants, followed by bacteremia (1.3%), osteomyelitis (0.24%), and meningitis (0.12%). Pneumococcus was the most common organism associated with bacteremia (46%), followed by Salmonella species (36%). All the children recovered.

The authors concluded that as the prevalence of SBI continues to decline in patients with SCD, ambulatory management using empirical antibiotics often is appropriate.

Before we had the many immunizations now available, as well as ceftriaxone, febrile children with SCD were hospitalized for several days routinely, regardless of how well they appeared. This study offers further support for treating such children as outpatients, provided they do not appear toxic and one can establish good follow-up.

Frequency of serious bacterial infection among febrile sickle cell disease children in the era of the conjugate vaccine: A retrospective study. 

International Journal of Pediatrics and Adolescent Medicine. 

Published online May 31, 2022. doi:10.1016/j.ijpam.2022.05.002

With instances of SBI lowering in children with sickle cell disease, authors of a recent study recommended continued management through empirical  antibiotics.

Prevalence of SBI in children with sickle cell disease continues to decline

MRI revealed inflammatory features in the ankle and midfoot of children with a clinical diagnosis of arthritis, not only in those with juvenile idiopathic arthritis (JIA), but also in those who did not have a final JIA diagnosis, according to a retrospective case-control study.

The single-center study was conducted at a center for pediatric rheumatology in Poland in 44 children aged 5 to 16 years (35 girls and 9 boys) with clinically suspected active ankle arthritis. Participants’ symptoms included ankle pain, swelling, tenderness, or limitation of movement associated with pain persisting more than 6 weeks. All participants underwent an MRI of the ankle that covered the area from the tibiotalar joint to the metatarsophalangeal joints.

JIA was confirmed in 22 (50%) of study group participants, including 14 patients with oligoarthritis, 6 with undifferentiated JIA, 1 with systemic JIA, and 1 with enthesitis-related arthritis. More lesions were identified in the JIA group than in the non-JIA group, with only 6 children free of lesions: 2 (4.5%) in the JIA group and 4 (9.0%) in the non-JIA group. MRI revealed inflammatory features in 38 (86%) of total study patients. No significant differences were found in either gender or mean age between the JIA group and the non-JIA group. The duration of arthritis in JIA patients ranged from 5 to 144 months (mean, 35.41 months) and in non-JIA patients from 6 to 36 months (mean, 17.6 months).

The most common findings in both groups were effusion in the tibiotalar joint (68% in the JIA group vs 64% in the non-JIA group) and effusion in the subtalar joint (64% vs 59%, respectively). However, tenosynovitis was the only lesion that was significantly more common in the JIA group than in the non-JIA group. In addition, advanced active inflammatory lesions were diagnosed in more than half (55%) of the JIA group and in none of the non-JIA group.

JIA remains an elusive diagnosis to pin down at times; it traditionally is based on a variety of factors, with no pathognomonic findings. There may be valid reasons for ordering an MRI of the ankle in these patients, but using the MRI to make a diagnosis is not one of them.

Ostrowska M, Michalski E, Gietka P, Mańczak M, Posadzy M, Sudoł-Szopińska I. Ankle magnetic resonance imaging in juvenile idiopathic arthritis versus non-juvenile idiopathic arthritis patients with arthralgia. 

. 2022;11(3):760. doi:10.3390/jcm11030760

In a recent study, rate of ankle arthritis did not differ significantly between children with JIA and children without JIA.

Ankle arthritis is not specific to JIA diagnosis

A retrospective study found that young women (postmenarchal) with a renal anomaly (RA) also were at risk of having a Müllerian anomaly (MA). The study group included 326 patients with an RA in whom a pelvic examination revealed a coexisting MA in 125 (38.3%). Of those who underwent the pelvic exam because of pain, about one-third were found to have an MA. The average age for RA diagnosis was 6.4 years and for MA diagnosis 16.4 years. Of the patients with obstructive MAs, 93.8% underwent urgent surgery, with the others started on hormonal suppression.

Patients with what investigators termed “solitary kidney” (true renal agenesis and involuted early multicystic dysplastic kidney [MCDK]) were most likely also to have an MA. In these patients, MA prevalence was 67% and included a 30% risk of an obstructive anomaly. Solitary kidney was the most common RA diagnosis in the study group, seen in 37.6%, but persistent MCDK also posed a 20% to 23% risk of an MA.

These findings support routine screening for an MA in patients with an RA, especially those with a congenital solitary kidney, the authors noted.


There has been controversy over the years about kidney disease and associated conditions (should we image the kidneys in children with isolated preauricular pits?), but this looks to have a more solid evidence base. For technical reasons, screening is best done shortly after menarche. Note that hydronephrosis is not one of the renal disorders that predisposes to MAs.

Fei YF, Smith YR, Wan J, Dendrinos M, Winfrey OK, Quint EH. Should we screen for Müllerian anomalies following diagnosis of a congenital renal anomaly? 

. 2022;S1477-5131(22)001164-4. doi:10.1016/j.jpurol.2022.04.017

A retrospective study found that postmenarchal women with a renal anomaly were also at risk of having a Müllerian anomaly. 

A renal anomaly? Look for a Müllerian anomaly as well 

Treatment of the various types of spinal muscular atrophy (SMA) with approved therapies results in an array of improvements, according to a review of 22 studies that assessed mid- and long-term (at least 12 months) outcomes in patients with SMA. Three therapies are approved for SMA: nusinersen, onasemnogene abeparvovec, and risdiplam, used alone or in combination, depending on the patient’s SMA type and other factors.

The analysis showed that nusinersen improved motor functions in patients with SMA type 1, while in SMA type 2 to type 4 disease this treatment was associated with patient stabilization or small improvements, though investigators also observed some deterioration. Onasemnogene abeparvovec improved motor functions (such as the ability to sit for at least 30 seconds or stand without support) in patients with SMA type 1, as did combination therapies in these patients. Procedure-related adverse events, generally caused by the lumbar puncture, were reported, though drug-related such events were rare. The authors noted, however, that the studies they reviewed either did not address pulmonary outcomes or reported on them “poorly.”


SMA is a disease we will start diagnosing earlier due to newborn metabolic screening. We now have options for this heretofore untreatable condition. The treatments look beneficial in at least the short term and it is hoped that better data will confirm their value long term, but for now I will cautiously classify them as “promising.”


Erdos J, Wild C. Mid- and long-term (at least 12 months) follow-up of patients with spinal muscular atrophy (SMA) treated with nusinersen, onasemnogene abeparvovec, risdiplam or combination therapies: a systematic review of real-world study data. 

 2022;39:1-10. doi:10.1016/j.ejpn.2022.04.006

Treatment of the various types of spinal muscular atrophy with approved therapies resulted in an array of improvements, according to a review of 22 studies.

Treatments alter the natural progression of SMA

The short answer to this question appears to be no based on an investigation of associations between patterns of growth in infant weight and adult-onset coronary heart disease (CHD).

Using data from national health registers, investigators in Denmark followed 3645 people who were born between 1959 and 1961 for whom they had weight information at birth, at aged 2 weeks, and at aged 1, 2, 3, 4, 6, and 12 months. They then generated 5 sex-specific weight trajectories of infant weight development: very low-moderate increase (11.5% of the study population), low-marked increase (13.9%), low-stable increase (32.4%), average-stable increase (29.8%), and high-moderate increase (12.4%).

Investigators also examined parental socioeconomic and marital status, maternal prepregnancy body mass index (PP-BMI), maternal smoking, parity, birth weight, and gender. Infants in the very low-moderately increasing trajectory group were more often boys, had mothers who had more babies, and had a lower gestational age than those in other trajectory groups. Also, the mothers of the infants in the very low-moderately increasing weight group were more likely to be married, had a lower PP-BMI, and smoked more during pregnancy than the other mothers.

During follow-up, at a median of 31.4 years, 279 people (159 men and 120 women) received a diagnosis of CHD. Individuals with a very low-moderately increasing trajectory developed CHD more often than those with an average-stable increasing trajectory. Though this association persisted after adjustment for maternal factors, it decreased after additional adjustment for preterm birth and parity. Further, the association completely disappeared after adjustment for birth weight. Investigators therefore determined that though very low-moderate increasing weight during infancy was associated with more likelihood of adult CHD, this association was driven by differences in birth weight, not infant weight gain. These findings, they noted, highlight the importance of prenatal exposures.


This is a large and very long-term study. I find it difficult enough to win the weight battle with children in elementary school and up. It’s good to know that I do not seem to have to work on this in plump babies but can let them grow naturally.

 
Blond K, Jensen BW, Petersen J, Baker J, Bjerregaard LG. Trajectories of infant weight gain from birth to 12 months and adult-onset coronary heart disease. 

 2022;S0022-3476(22)00305-5. doi:10.1016/j.jpeds.2022.03.055

Based on an investigation of associations between patterns of growth in infant weight and adult-onset coronary heart disease, the answer seems to be no. 